Shen Weifeng, Zhou Hui, Wang Wei, Li Wei
Department of clinical laboratory, The Affiliated Hospital of Jiaxing University, Jiaxing, China.
Jiaxing Key Laboratory of Clinical Laboratory Diagnosis and Transformation Research, The Affiliated Hospital of Jiaxing University, Jiaxing, China.
AMB Express. 2025 Apr 9;15(1):63. doi: 10.1186/s13568-025-01873-x.
Although some studies have reported a possible association between lipid and the development and progression of syphilis, the overall causal relationship between lipid and syphilis remains unclear. Data abstracted from extensive genome-wide association studies were utilized to pinpoint genetic variations linked to 179 distinct lipid species. Subsequently, these variations served as instrumental variables in Mendelian Randomization (MR) analyses, aimed at evaluating the causal impact of these lipid species on the occurrence of syphilis. A range of methods, including Weighted Mode, Weighted Median, Simple Mode, MR Egger, and Inverse Variance Weighted, were employed to determine the causal influence. For the purpose of sensitivity analysis, techniques such as Inverse Variance Weighted, MR-Egger, the MR Steiger test, the MR-Egger Intercept Test, and MR-PRESSO were applied. Additionally, Multivariate Mendelian Randomization (MVMR) analyses were conducted to directly assess the causal effect of lipid species on the risk of syphilis. Sterol ester (SE) and phosphatidylcholine (PC) could potentially impact syphilis risk. Specifically, SE (27:1/16:0), SE (27:1/18:2), SE (27:1/18:3), SE (27:1/20:3), and SE (27:1/22:6) were linked to an elevated risk of syphilis. PC (18:2_0:0) was linked to an elevated risk of syphilis. In contrast, PC (16:1_18:0) exhibited a protective role against syphilis. No heterogeneity or horizontal pleiotropy was detected. SE (27:1/16:0), SE (27:1/18:2), SE(27:1/18:3), SE (27:1/20:3), and SE (27:1/22:6) were no longer significantly associated with syphilis in the MVMR analysis (P>0.05). In addition, the previously observed effect of PC (18:2_0:0) on syphilis in univariate MR Was no longer significant in MVMR analysis. However, genetically predicted PC (16:1_18:0) was still significantly negatively associated with syphilis, consistent with univariate MR analysis. We observed that hereditary SE and PC levels appear to be associated with syphilis susceptibility. Future research is needed to understand the mechanisms behind this supposed causation and to develop corresponding treatment strategies.
尽管一些研究报告了脂质与梅毒的发生和发展之间可能存在关联，但脂质与梅毒之间的整体因果关系仍不明确。从广泛的全基因组关联研究中提取的数据被用于确定与179种不同脂质种类相关的基因变异。随后，这些变异在孟德尔随机化（MR）分析中作为工具变量，旨在评估这些脂质种类对梅毒发生的因果影响。采用了一系列方法，包括加权模式、加权中位数、简单模式、MR埃格检验和逆方差加权法，来确定因果影响。为了进行敏感性分析，应用了逆方差加权法、MR-埃格检验、MR斯泰格检验、MR-埃格截距检验和MR-PRESSO等技术。此外，还进行了多变量孟德尔随机化（MVMR）分析，以直接评估脂质种类对梅毒风险的因果效应。甾醇酯（SE）和磷脂酰胆碱（PC）可能会影响梅毒风险。具体而言，SE（27:1/16:0）、SE（27:1/18:2）、SE（27:1/18:3）、SE（27:1/20:3）和SE（27:1/22:6）与梅毒风险升高有关。PC（18:2_0:0）与梅毒风险升高有关。相比之下，PC（16:1_18:0）对梅毒具有保护作用。未检测到异质性或水平多效性。在MVMR分析中，SE（27:1/16:0）、SE（27:1/18:2）、SE（27:1/18:3）、SE（27:1/20:3）和SE（27:1/22:6）与梅毒不再有显著关联（P>0.05）。此外，在单变量MR中先前观察到的PC（18:2_0:0）对梅毒的影响在MVMR分析中不再显著。然而，基因预测的PC（16:1_18:0）仍与梅毒显著负相关，这与单变量MR分析一致。我们观察到遗传性SE和PC水平似乎与梅毒易感性有关。未来需要开展研究以了解这种假定因果关系背后的机制，并制定相应的治疗策略。
